A substantial body of prior art has evolved over the last decade involving compounds of 4-aryl-1,4-dihydropyridine series which have calcium antagonist properties and are useful in the treatment of cardiovascular diseases. These calcium blocking effects appear to mediate vasodilation which makes these compounds useful in treating angina and hypertension. These structures are typified by nifedipine (Formula 1); ##STR2## chemically, 4-(2'-nitrophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine. Nifedipine and some related 4-aryl-1,4-dihydropyridines are the subject of U.S. Pat. No. 3,485,847 issued Dec. 23, 1969. Numerous subsequent patents have been granted covering 1,4-dihydropyridines in which other substituent groups have been employed in the various ring positions of the dihydropyridine moiety. The structure of these later patented compounds which relate to the instant invention can be represented by Formula 2. ##STR3##
Bossert, et al, U.S. Pat. No. 3,488,359 patented Jan. 6, 1970 and U.S. Pat. No. 3,574,843 patented Apr. 13, 1971 disclose compounds where the variation involves R.sup.2 and R.sup.4 being alkoxyalkyl groups.
Murakami, et al, Ger. Offen. No. 2,407,115 disclose compounds where R.sup.2 is a disubstituted aminoalkyl group.
Kojima, et al, U.S. Pat. No. 4,220,649 patented Sept. 2, 1980 disclose compounds in which R.sup.2 is a pyrrolidine ring.
Loev, et al, U.S. Pat. No. 3,511,847 patented May 12, 1970 list compounds having extensive variation in the nature of R.sup.3. Also, the carboxyl groups which bond to R.sup.2 and R.sup.4 are replaced by carbonyl groups in the disclosure but these compounds are not claimed nor is any preparative method given for their synthesis.
Teulon, et al, U.S. Pat. No. 4,096,270 patented June 20, 1978 disclose dihydropyridines where R.sup.3 is a substituted pyridine moiety.
In summary, these and other earlier patented dihydropyridine compounds which relate to the instant invention can be represented by Formula 2. In general, R.sup.1, R.sup.2, R.sup.4, and R.sup.5 are alkyl groups or alkyl groups bearing miscellaneous substituents, e.g. amine, ether, mercapto groups, etc. The nature of R.sup.3 varies extensively but useful cardiovascular properties seem maximized when this group is an electron withdrawing aryl or heterocyclic moiety.
Meyers and Gabel reported in Heterocycles, Vol. 11, pages 133-138 (1978) a new synthesis of 1,4-dihydropyridines. This synthesis utilizes oxazolines as activating groups to facilitate organo metallic addition to the pyridine ring to yield 1,4-dihydropyridines (Formula 3). ##STR4## No utility was given for these compounds and they were usually converted to pyridines under mild oxidative conditions.